Numerous novel approaches to cancer therapy are currently being examined including gene therapy, immunotherapy and combinations of traditional and novel therapies. By targeting multiple events in the proliferation and spread of cancer cells the effectiveness of treatments may be improved and resistance to therapy avoided. Since SF/HGF may promote tumor growth through multiple actions both on cancer cells as well as endothelial cells in the vasculature supplying the tumors., it provides an excellent therapeutic target. Many glioma cell lines contain c-met, the receptor for SF/HGF and are therefore promising targets for SH/HGF antagonism. In addition SF/HGF antagonists would also prevent proliferation of endothelial cells which are more easily accessible than tumor cells, may be targeted specifically without significant side effects, are not likely to develop drug resistance because of their genetic stability and can be targeted for different tumor types. The current grant proposes to use the novel approach of inhibition of the angiogenic and growth activities of scatter factor/hepatocyte growth factor (SF/HGF) using small molecules designed by phase display and computer modeling in order to inhibit cancer growth and enhance the effectiveness of chemotherapy. In these studies we will continue development of a compound we have already identified with SF/HGF antagonistic activity and pursue a directed screening process to identify additional SF/HGF antagonists with the goal of improved efficacy and minimal toxicity. PROPOSED COMMERCIAL APPLICATIONS: The Phase I and Phase II projects are designed to provide the key pre- clinical data to support regulatory filing and launch of clinical trials of SF/HGF and mimetic molecules for therapeutic angiogenesis. The company expects to pursue clinical development and commercialization with a pharmaceutical industry partner.